The present invention pertains generally to absorbable coatings and absorbable blends for surgical sutures and drug delivery systems. More particularly, the invention relates to absorbable compositions which might include a homopolymer of .epsilon.-caprolactone and a crystallization modifier or a copolymer of .epsilon.-caprolactone, an absorbable monomer, and a crystallization modifier.
During the past thirty years, the use of synthetic absorbable polymers in medical devices and drug delivery systems has made a dramatic rise. Foremost in the area of absorbable medical devices has been the usage of absorbable polyesters that are usually aliphatic and linear. For example, in the area of wound closure, there has been extensive application of the homopolymer poly(glycolic acid), see for example U.S. Pat. No. 3,297,033, and copolymers of glycolic acid with a variety of other monomers which produce likewise absorbable polymers, see for example U.S. Pat. No. 3,839,297.
Dependent upon the specific application, there is a preferred time window where the synthetic polymer has completely absorbed, that is, has lost all of its mass to the surrounding tissue. In the case of absorbable sutures in sewn tissue after surgery, that window is usually within one year, although even shorter times are more preferable (U.S. Pat. Nos. 4,027,676 and 4,201,216). For other applications this time window could be either shorter or longer. Thus, for a given application there is a need to use absorbable polymers that degrade within the time limits of that application.
There is some leeway in the selection of synthetic absorbable polyesters for a given application since the rates of the hydrolysis of this class of polymers do vary over a wide range. Differences in the rates of hydrolysis of absorbable synthetic polyesters can be attributed to the intrinsic hydrolytic stability of their specific ester linkages and to the physical properties of their respective polymers. For instance, the hydrolytic stability of the ester linkage is strongly influenced by both electronic and steric factors. An example of an electronic effect is the increased reactivity of ester linkages which have a hydroxy substitution .alpha. to the ester linkage, as in the case of esters of glycolic acid. Physical properties which are important to the hydrolytic behavior and subsequent mass loss in synthetic absorbable polyesters include the glass transition temperature and the degree of crystallization in the polymer. In semi-crystalline polymers like poly(glycolic acid) and polycaprolactone, it has been hypothesized that hydrolysis takes place initially in the amorphous areas of the polymer, where migration or absorption of the water molecule is facile compared to the crystalline areas. Thus it appears that the water molecule prior to reaction at an ester linkage of synthetic absorbable polyester must first have access or absorption into the polymer. Crystalline areas of the polymer have been hypothesized to impede the access or penetration of water molecules. Therefore, to the extent that this takes place, the overall hydrolytic breakdown of the absorbable polyester is retarded. In the case of polycaprolactone, the hydrolytic degradation rate and subsequent mass loss is also dependent upon particle size, wherein small particles degrade and lose mass much more rapidly than a polymer cast in film form.
One application of synthetic polyesters is in the coating of surgical sutures. The coating on a surgical suture is very important in providing good knotting performance, as explained in U.S. Pat. No. 3,390,681, where the snug down performance of a braided non-absorbable poly(ethylene terephthalate) suture under both dry and wet conditions was improved by deposition of small particles of non-absorbable polytetrafluoroethylene. Tie-down performance of braided polyethylene terephthalate has also been disclosed to be improved through its coating with linear polyesters (U.S. Pat. No. 3,942,532) such as polycaprolactone. It was further disclosed in U.S. Pat. No. 3,942,532 that polycaprolactone of molecular weight in the range of 1,000 to 15,000 may also be used to coat synthetic absorbable sutures. However, polycaprolactone is known to be a slowly absorbable synthetic polyester, that may not meet the absorption time window, as it is known in the art, for an absorbable suture. Indeed, in subsequent U.S. Pat. Nos. 4,027,676 and 4,201,216 it is pointed out that the disclosure of linear polyesters for use with absorbable sutures in U.S. Pat. No. 3,942,532 did not consider that the sutures would not be totally absorbable. On the other hand, high molecular weight polycaprolactone has been disclosed in U.S. Pat. No. 4,624,256 to provide improved tie down performance and knot security to braided multifilament poly(glycolic acid) sutures under both dry and wet conditions. Thus, the art clearly demonstrates the usefulness of polycaprolactone as a coating for sutures in terms of tie-down performance and knot security. However, the use of an absorbable polymer must be matched with its allowable time window for complete absorption for a given application. Thus there is a need to be able to regulate the in vivo absorption profile of absorbable polymers to meet the criteria of specific applications.
An object of the invention is to increase the in vivo absorption rate of polycaprolactone by blending it with crystallization modifiers that reduce the amount of crystallinity in the polymer. Thus its rate of hydrolysis and subsequent mass loss can be regulated in order to meet the needs of a specific application. A further object of the invention is to provide an absorbable coating for absorbable sutures which meets the time window of complete absorption within-one year of surgery and provides good tie-down performance under both dry and wet conditions. An additional object of the invention is to provide a controlled absorbable matrix for the controlled release of chemical or pharmaceutical agents.